Permanently aligned multi-line lasers: A simplified solution for optical integration in biomedical instrumentation and fluorescence microscopes

摘要

The integration of multi-color laser excitation into biomedical instrumentation is associated with several challengeswhich must be overcome to meet the desired performance requirements of the instrument. Multi-color lasers are neededin fluorescence-analysis based applications such as flow cytometry, DNA sequencing, and various types of fluorescencemicroscopes such as scanning confocal microscopes, TIRF, Light-sheet, SIM, STORM and STED techniques. In manycases, these techniques require capability for excitation of multiple fluorophores and therefore access to several laserlines within the instrument.The advantages of lasers over other light-sources, such as LEDs, for these techniques are high-brightness and wavelengthprecision. Unfortunately, the inclusion of lasers also introduces complexity in the design. Laser combiners includingindividual lasers have been integrated with the intention of simplifying the design, as an alternative to traditional multilinegas lasers. This solution, however, is still susceptible to misalignment over time, and can increase the size and costof the instrument.A compact, permanently aligned, multi-line laser simplifies the integration of multiple laser wavelengths by eliminatingthe need for in-field alignment and service, reducing manufacturing cost, and allowing for more compact designs.In addition to overcoming the initial design challenges of integrating lasers into bio-instrumentation, a multi-line laser isalso an easy-to-upgrade field replacement for previous generations of technology, such as Argon Ion gas lasers.Here we demonstrate how a compact and robust permanently aligned multi-line solid-state laser can be achieved usingnovel techniques for optical assembly and miniaturization. We also show how the integration of such a multi-line lasercan deliver the required optical performance while simplifying the design and enabling commercialization of a newbioimaging technology, and exemplify the integration of this solution as a drop-in replacement for an Argon Ion lasers inexisting microscope set-ups.